Leber's hereditary optic neuropathy (LHON) is a genetic disease associated with mutations in mitochondrial DNA. The mutation has variable penetrance, but in many cases leads to severe and bilateral loss of vision in young adults. In this revision, the investigator and his senior collaborators propose to test the feasibility of delivering, expressing, and targeting normal gene products to mitochondria with the long-term objective of devising therapies for mitochondrial diseases. A recombinant adeno-associated virus (AAV) bearing a green fluorescent protein (GFP) gene and mitochondrion-specific targeting/processing signal sequences will be used to test whether proteins can be delivered safely, efficiently, and effectively into mitochondria in a cell culture system. This in vitro analysis will be followed by in vivo transduction experiments in which an attempt will be made to deliver a safe dose of a wild type NADH dehydrogenase to mitochondria in the retina and optic nerve of rats.